Endoscopic applicator with reagent ball cutter

ABSTRACT

A medical dispensing device which includes a catheter, an applicator tip at a distal end of the catheter, the catheter and the applicator tip defining a lumen having a longitudinal axis and a distal opening, a plunger in the lumen and movable along the longitudinal axis, and a plurality of elements in the lumen proximal to the distal opening and distal to the plunger, the plurality of elements stacked along the longitudinal axis for dispersement of one element at a time through the distal opening via a force applied by the plunger.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.16/860,252, filed Apr. 28, 2020, and now U.S. Pat. No. 11,554,251, whichclaims the benefit of priority from U.S. Provisional Application No.62/840,734, filed Apr. 30, 2019, each of which is incorporated byreference herein in its entirety.

TECHNICAL FIELD

The present disclosure relates generally to medical systems and devicesfor delivering protective barriers to the gastrointestinal (GI) region,and more particularly, to methods and tools for delivering and deployingpatches or other tissue barriers to the gastrointestinal system.

BACKGROUND

Conventional endoscopic procedures, such as endomucosal resection (EMR),endosubmucosal dissection (ESD), and anastomosis, as well as diseases,such as inflammatory bowel disease (IBD) and IBD subsidiary diseases,result in damage to GI tissues. These procedures and diseases cause verythin layers in the GI tract wall, leaving the GI tract wall vulnerableto GI perforation or other trauma.

Current procedures for repairing the GI tract require surgicalprocedures, including clipping or endoscopic suturing, to appose tissueand allow time for healing. These conventional techniques and associatedtechnologies are not suitable for large defects, or for repair offriable or fibrotic tissue. Yet, failure to provide a protective barrierbetween the damaged GI tract lining and the GI cavity can causeperforation, infection, and/or sepsis. The present disclosure may solveone or more of these problems or other problems in the art. The scope ofthe disclosure, however, is defined by the attached claims and not theability to solve a specific problem.

SUMMARY OF THE DISCLOSURE

According to an embodiment, a medical dispensing device comprises acatheter defining a lumen having a longitudinal axis and a distalopening, a plunger disposed in the lumen and movable along thelongitudinal axis, and a plurality of elements disposed in the lumenproximal to the distal opening and distal to the plunger, the pluralityof elements being stacked along the longitudinal axis for dispersementone element at a time through the distal opening via a force applied bythe plunger.

The device may include a wire or a cable disposed in the lumen andconnected to a proximal end of the plunger, and the wire or the cablemay be configured to move the plunger axially along the longitudinalaxis.

The plurality of elements may include a plurality of stacked patches,and each of the plurality of stacked patches may have an adhesive layerand a non-adhesive layer proximal to the adhesive layer.

The non-adhesive layer may be configured to remain attached to theadhesive layer after dispensing the respective patch from the device.

The non-adhesive layer may not extend across an entire proximal surfaceof the adhesive layer, exposing a portion of the proximal surface of theadhesive layer, and the exposed portion of the proximal surface may beattached to (1) a distal surface of the adhesive layer of an adjacentand proximal patch from the plurality of stacked patches, or (2) theplunger.

A proximal surface of the non-adhesive layer of a distalmost patch ofthe plurality of stacked patches may be configured to contact adistalmost surface of the catheter outside of the lumen.

The device may include a second wire or a second cable extending from aproximal end to a distal end of the catheter and may be attached to eachof the non-adhesive layers, and may be configured to remove eachseparate non-adhesive layer from a corresponding adhesive layer.

The device may include a second lumen defined by the catheter, thesecond wire or the second cable may extend through the second lumen, andthe second lumen may receive each of the non-adhesive layers separatefrom the corresponding adhesive layer.

Each of the adhesive layers may include one or more therapeutic agents.

The distal end of the catheter may include an annular ring at adistalmost portion of the catheter and extending from a sidewall of thecatheter toward the distal opening, wherein a distance between aninnermost surface of the annular ring and the longitudinal axis may beless than a distance between an innermost surface of the sidewall of thecatheter and the longitudinal axis.

A distal surface of a distalmost element of the plurality of elementsmay be configured to contact a proximal surface of the annular ring, andthe force applied by the plunger may push the distalmost element out thedistal opening.

The device may include a wall disposed in the lumen, transverse to thelongitudinal axis, and fixed to a sidewall of the lumen at a locationproximal to the plurality of elements, and may include a biasing elementattached at a first end to the wall, and at a second end to the plunger,such that a force provided by the biasing element may push the plungeragainst the plurality of elements and toward the distal opening.

The plurality of elements may include a plurality of deformable spheres,an outer surface of each of the deformable spheres including a firstmaterial and surrounding and containing therein a second material,different from the first material.

A protrusion may extend from a sidewall defining the lumen toward thelongitudinal axis, and distal to a distalmost one of the plurality ofdeformable spheres.

The device may include one or more cutters distal to the protrusion andextending from the sidewall defining the lumen toward the longitudinalaxis, wherein the one or more cutters may be configured to cut the outersurface of each of the plurality of deformable spheres and expose thesecond material as each of the plurality of deformable spheres isdispensed from the device.

According to another embodiment, a medical dispensing device includes ahandle, a catheter extending distally from the handle, an applicator tipat a distal end of the catheter, the catheter and the applicator tipdefining a lumen having a longitudinal axis and a distal opening, aplunger disposed in the lumen and movable along the longitudinal axis,and a plurality of elements disposed in the lumen proximal to the distalopening and distal to the plunger, the plurality of elements beingstacked along the longitudinal axis for dispersement one element at atime through the distal opening.

The plurality of elements may include a plurality of deformable spheres,an outer surface of each of the deformable spheres including a firstmaterial and surrounding and containing therein a second, flowablematerial, different from the first material.

The plurality of elements may include a plurality of stacked patches,each of the plurality of stacked patches may have an adhesive layer anda non-adhesive layer proximal to the adhesive layer.

According to yet another embodiment, a method for applying a medicalpatch to tissue includes pushing a stack of patches toward a distalopening of a catheter, moving the catheter toward a target, such that adistalmost patch from the stack of patches contacts the target, andmoving the catheter in a proximal direction, away from the target,thereby releasing the distalmost patch from the catheter.

The method may include, after releasing the distalmost patch from thecatheter, pushing the remaining patches of the stack of patches towardthe distal opening, moving the catheter toward a second target, suchthat a second distalmost patch contacts the second target, and movingthe catheter in a proximal direction, away from the second target,thereby releasing the second distalmost patch from the catheter

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings, which are incorporated in and constitute apart of this specification, illustrate various exemplary embodiments andtogether with the description, serve to explain the principles of thedisclosed embodiments.

FIG. 1 is a schematic of an endoscopic applicator system according to anembodiment;

FIG. 2 is a perspective view of a handle for an endoscopic applicatorsystem according to an embodiment;

FIG. 3 is a cross-section of an applicator tip according to anembodiment;

FIG. 4A is a perspective view of a handle for an endoscopic applicatorsystem according to an embodiment;

FIG. 4B is a cross-section of an applicator tip according to anembodiment;

FIG. 5A is a perspective view of a handle for an endoscopic applicatorsystem according to an embodiment;

FIG. 5B is a cross-section of an applicator tip according to anembodiment;

FIG. 6 is a schematic of an endoscopic applicator system according toanother embodiment;

FIGS. 7A-7C are cross-sections of an applicator tip according to anotherembodiment;

FIG. 8A is a cross-section of an applicator tip according to yet anotherembodiment;

FIG. 8B is a cross-section of a regenerative patch according to anembodiment;

FIG. 9 is a cross-section of an applicator tip according to yet anotherembodiment;

FIGS. 10A-10D are cross-sections of an applicator tip according toanother embodiment;

FIGS. 11A-11B are cross-sections of an applicator tip according to yetanother embodiment; and

FIGS. 12A-12B are cross-sections of an applicator tip according to yetanother embodiment.

DETAILED DESCRIPTION

Both the foregoing general description and the following detaileddescription are exemplary and explanatory only and are not restrictiveof the features, as claimed. As used herein, the terms “comprises,”“comprising,” “having,” “including,” or other variations thereof, areintended to cover a non-exclusive inclusion such that a process, method,article, or apparatus that comprises a list of elements does not includeonly those elements, but may include other elements not expressly listedor inherent to such a process, method, article, or apparatus. In thisdisclosure, relative terms, such as, for example, “about,”“substantially,” “generally,” and “approximately” are used to indicate apossible variation of ±10% in a stated value or characteristic.

Referring to FIG. 1 , an endoscopic applicator 10 according to anembodiment is shown. Endoscopic applicator 10 includes a handle 20, acatheter 30 connected to handle 20, and an applicator tip 40 at a distalend of catheter 30, opposite handle 20.

FIG. 2 illustrates handle 20 according to an exemplary embodiment.Handle 20 includes a body 22 defining a hole 22 a in body 22 at aproximal end thereof. Catheter 30 is attached at an opposite, distal endof body 22. A slot 26 extends through body 22 in a direction parallel toa direction of extension of catheter 30. A spool 24 is disposed in slot26 and moves within and along slot 26 in a direction parallel to thedirection of extension, as shown by arrow A. As further shown in FIG. 2, spool 24 includes two annular protrusions 24 a at a distal end and aproximal end thereof and extending from spool 24 in a directionperpendicular to the direction of extension of catheter 30. Annularprotrusions 24 a define an annular grip 24 b, which is grasped by a useras will be described in greater detail herein. It will be understoodthat handle 20 may be made of any material known in the art, including,but not limited to, a medical grade plastic or rubber, a ceramic, ametal, or a combination thereof.

As further shown in FIG. 2 , a wire 32 (or a cable) extends distallyfrom the distal end of spool 24. Wire 32 extends through a hole (notshown) in handle 20 and into a lumen 36 (FIG. 3 ) of catheter 30. Aswill be described in greater detail herein, actuation of wire 32dispenses a regenerative patch. As will be understood, catheter 30 is agenerally circular sheath extending from handle 20 to applicator tip 40.While catheter 30 is described as including lumen 36 (FIG. 3 ), catheter30 may include multiple lumens to incorporate other tools and/orelements (e.g., lighting, imaging, etc.) at applicator tip 40.Additionally, or alternatively, catheter 30 may be placed in another,larger catheter or endoscope (not shown), if use of tools, suction,light-emitting elements, or the like associated with the larger catheterare so desired. It will be understood that wire 32 may include anymaterial known in the art, including, but not limited to, medical gradeplastic, metal, or other resin suitable to be used to push and/or pull aplunger 34 (FIG. 3 ), as described herein, during application of aregenerative patch or agent. It will be understood that while examplesdiscuss a regenerative agent applied to a patch, the patch may includean adhesive without a regenerative agent. Further, it will be understoodthat catheter 30 may be formed of any medical grade plastic, rubber,resin, or the like that is suitable for use in medical applications.

Referring to FIG. 3 , which shows a cross-section of applicator tip 40,as indicated by the cross-sectional lines shown in FIG. 1 , applicatortip 40 is disposed at the distal end of catheter 30. Applicator tip 40includes an outer wall 42 having a generally circular cross-section. Asshown in FIG. 3 , applicator tip 40 is the distalmost portion ofcatheter 30, as applicator tip 40 may be integrally formed with catheter30. Applicator tip 40 further includes an annular ring 44 provided at adistalmost portion of applicator tip 40. Annular ring 44 extendsannularly from an outermost part of outer wall 42 toward a centrallongitudinal axis Z (e.g., central axis Z) of lumen 36, has a uniformthickness, and forms a radially-inward directed flange at the distalmostend of endoscopic applicator 10. The flange assists in retaining patcheswithin applicator tip 40. A distance from central axis Z to an innermostportion 44 a of annular ring 44 is less than a distance from centralaxis Z to an innermost portion 42 a of outer wall 42. Alternatively, oradditionally, applicator tip 40, including outer wall 42, may be aseparate element from catheter 30, such as an add on device attached viascrew threads, adhesive, snap fit, or the like. Applicator tip 40 may beany material known in the art, including, but not limited to, a medicalgrade plastic, resin, or rubber. Alternatively, any other mechanism forretaining patches 50, e.g., tabs, may be provided at the distalmostportion of applicator tip 40.

As shown in FIG. 3 , a stack of patches 50, for example patches having aregenerative agent, are disposed in applicator tip 40 for application toa target 60, as explained herein. Plunger 34, connected to a distalmostportion of wire 32, is disposed in applicator tip 40 at a positionproximal to the stack of patches 50. Plunger 34 may be any materialknown in the art, including, but not limited to a medical grade metalalloy, a plastic, a resin, or a rubber, suitable for being used to placepressure against the stack of patches 50.

With continued reference to FIG. 3 , the stack of patches 50 may includea first patch 51 a having a first layer 52 a including an adhesivesubstance and a second layer 54 a including a non-adhesive backing, sothat adjacent patches 50 do not adhere to one another. As describedherein, first layer 52 a may include a regenerative agent, an adhesiveregenerative agent, or any other therapeutic or diagnostic agent and/orattachment mechanism for attaching first patch 51 a to target 60.

First layer 52 a is provided at a distalmost position of lumen 36 and isadjacent to and in contact with annular ring 44 of applicator tip 40.First layer 52 a is applied to target 60, e.g., tissue, or anothersuitable target site, as will be described herein. A second patch 51 bhaving a first layer 52 b including an adhesive agent (and/or aregenerative agent) and a second layer 54 b including a non-adhesivebacking is disposed proximal to and adjacent second layer 54 a of firstpatch 51 a. A third patch 51 c having a first layer 52 c and a secondlayer 54 c is disposed proximal to and adjacent second layer 54 b ofsecond patch 51 b, and so on and so forth for n number of patches (an npatch 51 n is illustrated in FIG. 4B and has a first layer 52 n and asecond layer 54 n). It will be understood that target 60 may be anytissue known in the art, including but not limited to endomucosaltissue, gastrointestinal tissue, bone tissue, cartilage, etc.

An operation of endoscopic applicator 10 illustrated in FIGS. 1-3 willnow be described.

Endoscopic applicator 10 is introduced to the body through an opening,such as through the mouth or nose, or through an opening formed by anincision, e.g., during a surgical procedure. Applicator tip 40 isinserted into the body through the opening and advanced to the desireddeployment site, e.g., the GI tract. According to an embodiment,applicator tip 40 and catheter 30 are advanced along a guidewire (notshown). It will be understood that applicator tip 40 and catheter 30 maybe advanced along a pre-positioned sheath, catheter, endoscope,bronchoscope, colonoscope, or the like, e.g., a catheter with multiplelumens to provide light emission, suction, tools, or the like, or may bepositioned in any other manner or using any other device known in theart.

After positioning applicator tip 40 at the desired location, e.g., attarget 60, deployment and placement of the stack of patches 50,one-by-one in a serial fashion, is performed. Referring to FIGS. 4A and4B, handle 20 is maneuvered to push the distalmost portion of applicatortip 40, including annular ring 44, in a direction indicated by arrows B,such that annular ring 44 abuts target 60. At a same time, orsubsequently, spool 24 (grasped by an index finger and a middle fingerof the user's hand, while a thumb is in hole 22 a, for example) isadvanced longitudinally along handle 20 in a direction indicated byarrow C toward a distal end 20 a of handle 20, thereby pushing wire 32and plunger 34 in the direction indicated by arrow C in FIG. 4B. Plunger34 pushes against the proximalmost patch 51 n (n is a number of patchesin the stack of patches 50, and may be a maximum number of patches inthe stack of patches 50 that can be disposed in applicator tip 40),thereby forcing the stack of patches 50 against target 60, and causingfirst layer 52 a of first patch 51 a to contact and adhere to target 60.Subsequently, while continuing to push spool 24 toward distal end 20 aof handle 20, or maintaining a position of spool 24 relative to handle20, endoscopic applicator 10, including applicator tip 40, is pulled ina proximal direction, as indicated by arrow D in FIGS. 5A and 5B. Asshown in FIG. 5B, first patch 51 a adheres to target 60 via first layer52 a, and second layer 54 a remains attached to a side of first layer 52a opposite target 60. After application of first patch 51 a, applicatortip 40 is moved to another application location, e.g., a positionadjacent first patch 51 a, and the application of second patch 52 a isperformed. In this manner, one or more patches from the stack of patches50 is applied to target 60.

Referring to FIG. 6 , an endoscope applicator 110 according to anotherembodiment is disclosed. Like reference numerals will be used todescribe like elements.

Endoscope applicator 110 includes a handle 120, a catheter 130 attachedto handle 120, and an applicator tip 140 attached to catheter 130 at adistal end opposite handle 120. Spool 124 is shown in FIG. 6 ; however,since a spool is unnecessary in the operation of endoscope applicator110 according to the embodiment in FIGS. 6-7C as described herein,handle 120 may be formed without spool 124. With continued reference toFIG. 6 , catheter 130 is a generally circular sheath extending fromhandle 120 to applicator tip 140 and defining a lumen 136, similar tocatheter 30 described above.

Referring to FIG. 7A, applicator tip 140 according to an embodiment willbe described. Applicator tip 140 is disposed at a distal end of catheter130. Applicator tip 140 includes an outer wall 142 and an annular ring144, similar to applicator tip 40. As shown in FIG. 7A, a stack ofpatches 150 is disposed in applicator tip 140 for application to atarget 160, as explained herein. A plunger 146 is connected to a fixedplate 148 via a spring 147, all of which are disposed in applicator tip140 at a position proximal to the stack of patches 150. Fixed plate 148may have an area equal to or smaller than a cross-section area of lumen136 and may be fixed to a sidewall of lumen 136 via an adhesive, sonicwelding, or the like. Plunger 146, spring 147, and fixed plate 148 maybe any material known in the art, including but not limited to a medicalgrade metal alloy, a plastic, a resin, or a rubber, suitable for beingused to place pressure against the stack of regenerative patches 150 andpush the stack of patches 150 toward a distal opening of applicator tip140.

With continued reference to FIG. 7A, the stack of patches 150 mayinclude a first patch 151 a having a first layer 152 a including anadhesive substance and a second layer 154 a, including a non-adhesivesurface 154 a 1, so that adjacent patches 150 do not adhere to oneanother, and an adhesive surface 154 a 2, which may include the samematerial as first layer 152 a. As described herein, first layer 152 amay include a regenerative agent, an adhesive regenerative agent, or anyother agent and/or attachment mechanism for attaching first patch 151 ato target 160.

Prior to a first application, first patch 151 a is partially exposedfrom applicator tip 140, outside of the distal opening of the applicatortip 140 such that non-adhesive surface 154 a 1 is adjacent to and/orcontacts an outer surface of annular ring 144, thereby exposing firstlayer 152 a outside applicator tip 140, as will be described in greaterdetail herein. Adhesive surface 154 a 2 is attached to a first layer 152b of a second patch 151 b, as shown in FIG. 7A. Second patch 151 b alsoincludes a second layer 154 b having a non-adhesive layer 154 b 1 and anadhesive surface 154 b 2. A patch 151 n, which is a proximalmost patch,has an adhesive surface 154 n 1, which attaches to plunger 146 (n is anumber of patches in the stack of patches 150, and may be a maximumnumber of patches in the stack of patches 150 that can be disposed inapplicator tip 140). First layer 152 a is applied to target 160, e.g., atissue or another suitable target site, as will be described herein. Itwill be understood that target 160 may be any tissue known in the art,including but not limited to endomucosal tissue, gastrointestinaltissue, bone tissue, cartilage, etc.

An operation of endoscopic applicator 110 illustrated in FIGS. 7B and 7Cwill now be described. Endoscopic applicator 110 is introduced to thebody in a same manner an endoscopic applicator 10 in FIGS. 1-3 , asdescribed above. After positioning applicator tip 140 at the desiredlocation, e.g., at target 160, placement of one or more of the stack ofpatches 150 is performed. Handle 120 is maneuvered to push thedistalmost portion of applicator tip 140 in FIG. 7B, including annularring 144, in a direction indicated by arrow B and against target 160.Pushing applicator tip 140 against target 160 causes a surface of firstlayer 152 a, opposite a surface of second layer 154 a contacting annularring 144, to contact and adhere to tissue 160. Subsequently, as shown inFIG. 7C, applicator tip 140 is pulled in a direction indicated by arrowD, via handle 120, which causes the remainder of patch 151 a to exitapplicator tip 140. If necessary to completely deploy all of patch 151 aagainst target 160, handle 120 and applicator tip 140 are again moved inthe direction indicated by arrow B in FIG. 7B, such that annular ring144 presses against a surface 154 b 1 of second layer 154 b of secondpatch 151 b, as shown in FIG. 7B, causing first patch 151 a to adhere totarget 160. Applicator tip 140 is again moved in a direction indicatedby arrow D in FIG. 7C, which pulls first layer 152 b of second patch 151b from surface 154 a 2 of first patch 151 a. Spring 148 forces plunger146 against patch 151 n, thereby forcing the stack of regenerativepatches 150 toward the distal end of applicator tip 140, allowing secondpatch 151 b to be applied to the same target 160 or a different target.As shown in FIG. 7C, second patch 151 b is set to be applied to anotherlocation on target 160. As further shown in FIG. 7C, second layer 154 aremains attached to first layer 152 a, but the embodiment is not limitedto this configuration, since second layer 154 a may be released fromfirst layer 152 a during and/or subsequent to application of first patch151 a to target 160.

According to another embodiment, an applicator tip 240 is illustrated inFIG. 8A, and has similar features as applicator tip 40, described above.As shown in FIG. 8A, a stack of patches 250 is disposed in applicatortip 240 for application to a target 260, as explained herein. The stackof patches 250, including first patch 251 a having a first layer 252 aand a second layer 254 a, and including second patch 251 b having afirst layer 252 b and a second layer 254 b, are applied to target 260using a plunger 234 attached to a wire 232 in a manner as describedabove with reference to FIGS. 4A-5B. Applicator tip 240 according to anembodiment is used with, e.g., handle 20 shown in FIG. 2 .

An operation of an endoscopic applicator, such as endoscopic applicator10 in FIG. 1 , having an applicator tip 240 will now be described.Applicator tip 240 is inserted into the body through the opening andadvanced to the desired deployment site, e.g., the GI tract, as in theprevious embodiments. After positioning applicator tip 240 at thedesired location, deployment and placement of the stack of patches 250is performed, in any manner described above.

As shown in FIG. 8A, first patch 251 a adheres to target 260 via firstlayer 252 a. As shown in FIG. 8B, after first patch 251 a is attached totarget 260, second layer 254 a disengages or disconnects from, orotherwise falls off of, a back side (e.g., a side opposite target 260)and is passed from the body via normal excretion, is retrieved byanother tool, and/or is biodegradable. After application of first patch251 a, applicator tip 240 is moved to another application location,e.g., a position adjacent first patch 251 a, and the application ofsecond patch 251 b is performed. In this manner, one or more patches 251n from the stack of patches 250 is applied to the same target 260, or adifferent target. While handle 20, including spool 24, is described inthe operation of applicator tip 240, the application device (e.g.,spring 147, fixed plate 148, and plunger 146) illustrated in FIG. 7A mayalternatively be used with applicator tip 240 to advance patches 250along applicator tip 240 during application.

According to another embodiment, an applicator tip 340 is illustrated inFIG. 9 . Like reference numerals will be used to describe like elements.

Applicator tip 340 is disposed at a distal end of a catheter (such ascatheter 30 shown in FIG. 1 ). Applicator tip 340 includes an outer wall342 and an annular ring 344, like those in prior embodiments.

The stack of patches 350 includes a plurality of patches as describedherein. Each of the plurality of patches has a first layer, e.g., 352 a,and a second layer, e.g., 354 a. As shown in FIG. 9 , each second layer,e.g., 354 a, is attached to a pulley system 338, as will be describedherein.

As shown in FIG. 9 , a stack of patches 350 are disposed in applicatortip 340 for application to a target 360. One or more of patches 350 areapplied to target 360 using a plunger 334 attached to a wire 332disposed in a first lumen 336 a in a manner as described above withreference to FIGS. 4A-5B. First lumen 336 a and a second lumen 336 b mayinclude a pulley system, as shown in FIG. 9 . The pulley system mayinclude a wire or cable 338 that may extend around a pulley 339 at adistalmost end of applicator tip 340 and into a second lumen 336 b,adjacent first lumen 336 a, and which extends to a proximal end of acatheter, e.g., catheter 30 described herein. Cable 338 may attach toeach of the second layers (e.g., second layer 354 a) at connectionpoints 370. Alternatively, applicator tip 340 may be formed withoutsecond lumen 336 b, and cable 338 may extend on an outer side ofapplicator tip 340. As a further alternative, pulley 339 may be locatedwithin one or more lumens of the catheter so no parts of the pulleysystem are outside of the catheter. Cable 338 extends to a handle, e.g.,handle 20, to allow a user to manipulate cable 338, as will be describedherein. Applicator tip 340 according to an embodiment is used withhandle 20 shown in FIG. 2 .

An operation of an endoscopic applicator, such as endoscopic applicator10 in FIG. 1 , having an applicator tip 340 will now be described.Applicator tip 340 is inserted into the body through the opening andadvanced to the desired deployment site, e.g., the GI tract, in any ofthe manners described above. After positioning applicator tip 340 at thedesired location, deployment and placement of the stack of patches 350is performed, in any manner described above. As shown in FIG. 9 , firstlayer 352 a was previously adhered to target 360. Subsequently, whilecontinuing to push spool 24 toward distal end 20 a of handle 20, anendoscopic applicator (including handle 20, catheter 30, and applicatortip 340) is pulled in a proximal direction, as indicated by arrow D inFIG. 5A. As shown in FIG. 9 , first layer 352 a adheres to target 360.After first layer 352 a is attached to target 360, second layer 354 a,which is attached to cable 338, is detached from first layer 352 a andpulled proximally inside second lumen 336 b. Cable 338 may be operatedin any manner known in the art, for example by a user or by a motor (notshown). Alternatively, or additionally, cable 338 may pull second layer354 a on an external side of applicator tip 340.

After application of first layer 352 a, applicator tip 340 is moved toanother application location, e.g., a position adjacent first layer 352a, and the application of a first layer of second patch 351 b isperformed. In this manner, one or more patches from the stack of patches350 is applied to target 360. While handle 20, including spool 24, isdescribed in the operation of applicator tip 340, the application device(e.g., spring 147, fixed plate 148, and plunger 146) illustrated in FIG.7A may alternatively be used with applicator tip 340 to advance patches350 along applicator tip 340 during.

According to another embodiment, applicator tips 440 and 540 will bedescribed with reference to FIGS. 10A-11B.

As shown in FIG. 10A, an applicator tip 440 is disposed at a distal endof a catheter (such as catheter 30 shown in FIG. 1 ). Applicator tip 440includes an outer wall 442 having a generally circular cross-section.Applicator tip 440 is the distalmost portion of the catheter. Applicatortip 440 further includes a protrusion 444 extending into a lumen 436 ofapplicator tip 440. Protrusion 444 may be an annular protrusion, or oneor more protrusions, that extends over less than a full circumference oflumen 436. A distance from central axis Z to an innermost portion ofprotrusion 444 is less than a distance from central axis Z to aninnermost surface of outer wall 442. Protrusion 444 secures a pluralityof spheres or balls 450 in applicator tip 440 until a force applied tothe plurality of spheres 450, e.g., provided by a plunger 434, forcesthe distalmost ball past protrusion 444.

A stack of spheres 450 includes a plurality of spheres 452 a, 452 b,etc. as described herein. Each of the plurality of spheres, e.g., 452 a,452 b, has a reagent, e.g., 454 a (see FIG. 10D), provided within forapplication to a target 460. One or more of the stack of spheres 450 areapplied to target 460 using a plunger 434 in a manner as described abovewith reference to FIGS. 4A-5B. Applicator tip 440 according to anembodiment is used with handle 20 shown in FIG. 2 .

With reference to FIG. 11A, an applicator tip 540, similar to applicatortip 440, will be described. Applicator tip 540 is disposed at a distalend of a catheter (such as catheter 30 shown in FIG. 1 ). Applicator tip540 includes an outer wall 542 and a protrusion 544, like those in priorembodiments. Applicator tip further includes one or more blades 546 (orother cutting elements) distal of annular protrusion 544. Blades 546 areused to cut through an outer shell, which may be a rigid or deformableshell containing a substance container therein, of each of the pluralityof spheres 550 during application to target 560, as described herein.

The plurality of spheres 550 include, e.g., spheres 552 a, 552 b, etc.,and including a reagent, e.g., 554 a, as described herein with referenceto applicator tip 440.

An operation of applicator tip 440 and 540 will now be described withreference to FIGS. 10A-10D and 11A-11B. Applicator tips 440 or 540 areinserted into the body through the opening and advanced to the desireddeployment site, e.g., the GI tract, in any of the manners describedabove. After positioning applicator tips 440 and 540 at the desiredlocation, deployment and placement of the plurality of spheres 450 or550 is performed in any manner described above.

With reference to FIG. 10C, a first ball 452 a is forced from applicatortip 440 and against target 460. The pressure between first sphere 452 aand target 460 and/or applicator tip 440 causes first ball 452 a torupture, thereby releasing a first reagent 454 a, which coats target460. First reagent 454 a may be hydrophilic and or otherwise designed tobe attracted to target 460.

Dispensing the plurality of spheres 550 using applicator tip 540 may beperformed, as shown in FIGS. 11A and 11B. A first sphere 552 a is forcedpast annular protrusion 544 and out a distal end of applicator tip 540.As first ball 552 a is dispensed, an outer layer of first ball 552 a iscut by one or more blades 546, thereby releasing a first reagent 554 a,which coats target 560. After application of first reagents 454 a, 554a, applicator tips 440 or 540 are moved to another application location,e.g., a position adjacent the application area or another target area,and the application of another reagent using second spheres 452 b, 552 bis performed. In this manner, reagents from one or more spheres from thestack of spheres 450, 550 are applied to targets 460, 560, respectively.

According to another embodiment, an applicator tip 640 is illustrated inFIGS. 12A and 12B. Like reference numerals will be used to describe likeelements.

Applicator tip 640 is disposed at a distal end of a catheter (such ascatheter 30 shown in FIG. 1 ). Applicator tip 640 includes an outer wall642 having a generally circular cross-section and an annular ring 644,similar to applicator tip 40.

The stack of patches 650 includes a plurality of patches 651 a, 651 b,etc. as described herein. Each of the plurality of patches has a firstlayer, e.g., 652 a, and a spacer, e.g., 654 a. As shown in FIG. 12B,each spacer, e.g., 654 a, separates from each first layer e.g., 652 a,after application to target 660, as will be described herein.

As shown in FIG. 12A, a stack of patches 650 are disposed in applicatortip 640 for application to a target 660, as explained herein. The stackof patches 650 are applied to target 660 in any manner described above.For example, applicator tip 640 according to an embodiment is used withhandle 20 shown in FIG. 2 .

An application of the stack of patches 650 will be described withreference to FIGS. 12A and 12B. Applicator tip 640 is inserted into thebody through the opening and advanced to the desired deployment site,e.g., the GI tract, in any manner described herein. After positioningapplicator tip 640 at the desired location, deployment and placement ofthe stack of patches 650 is performed, similar to the manner describedwith respect to the embodiments above. After patch 651 a is attached totarget 660, first separator 654 a is detached from first layer 652 a.Separator 654 a may be biodegradable. Alternatively, or additionally,separator 654 a may be small enough to pass through the body and beexcreted during normal bowel movements by a patient, or may be removedby a tool.

After application of first patch 651 a, applicator tip 640 is moved toanother application location, e.g., a position adjacent first patch 651a or another target site, and the application of second patch 651 b isperformed. In this manner, one or more patches from the stack ofregenerative 650 is applied to target 660.

It will be understood that, unless specifically set forth herein, anymaterial known in the art may be used for the various elements. Forexample, features may include a medical grade plastic or rubber, aceramic, a metal, or a combination thereof. Spacers and/or separationlayers may be may include a material that is biodegradable and/or mayinclude one or more of a medical grade plastic or rubber, a ceramic, ametal, or a combination thereof, such as polyvinyl acetate (PVA),polyhydroxyethylmethacrylate (PHEMA), polytetrafluoroethylene (PTFE),HDPE (high-density polyethylene), polydimethylsiloxane (PDMS),polyurethane (PU), and/or poly(methyl methacrylate) (PMMA). Theattachment agent(s) may be one or more biocompatible materials and maybe adhesive prior to introduction into a body lumen and/or may beactivated by moisture. Further, the regenerative agent may include anadhesive agent as described above, and/or may be any agent now known orlater developed for the treatment of the inner walls of a human body,such as the GI tract.

It will be apparent to those skilled in the art that variousmodifications and variations can be made to the disclosed device withoutdeparting from the scope of the disclosure. Other embodiments of thedisclosure will be apparent to those skilled in the art fromconsideration of the specification and practice of the inventiondisclosed herein. It is intended that the specification and examples beconsidered as exemplary only, with a true scope and spirit of theinvention being indicated by the following claims.

What is claimed is:
 1. A medical dispensing device, comprising: acatheter defining a lumen having a longitudinal axis and a distalopening; a plunger disposed in the lumen and movable along thelongitudinal axis; a plurality of balls disposed in the lumen proximalto the distal opening and distal to the plunger, the plurality of ballsbeing stacked along the longitudinal axis for dispersement, one ball ata time, through the distal opening via a force applied by the plunger;and one or more cutting elements disposed at the distal opening, whereinthe one or more cutting elements is configured to cut an outer surfaceof each of the balls of the plurality of balls, and wherein the one ormore cutting elements includes one or more blades.
 2. The medicaldispensing device of claim 1, wherein the outer surface of each of theballs of the plurality of balls includes a first material surroundingand containing therein a second material, and wherein the secondmaterial is different from the first material.
 3. The medical dispensingdevice of claim 2, wherein the first material is one of a rigid shell ora deformable shell.
 4. The medical dispensing device of claim 2, whereinthe second material is one of a first reagent or a second reagent. 5.The medical dispensing device of claim 4, wherein a first subset of theplurality balls includes the first reagent, and wherein a second subsetof the plurality of balls includes the second reagent.
 6. The medicaldispensing device of claim 5, wherein each of the balls within the firstsubset is adjacent a ball of the second subset.
 7. The medicaldispensing device of claim 2, wherein the one or more cutting elementsis configured to cut the outer surface of each of the balls of theplurality of balls such that the second material is exposed as each ofthe balls of the plurality of balls is dispensed from the medicaldispensing device.
 8. The medical dispensing device of claim 1, whereina protrusion extends from a sidewall defining the lumen, toward thelongitudinal axis, and distal to a distalmost ball of the plurality ofballs.
 9. The medical dispensing device of claim 8, wherein the one ormore cutting elements is disposed distal to the protrusion.
 10. Themedical dispensing device of claim 8, wherein the one or more cuttingelements extends from the sidewall defining the lumen and toward thelongitudinal axis.
 11. The medical dispensing device of claim 8, whereinthe protrusion is configured to maintain a position of the plurality ofballs within the lumen.
 12. The medical dispensing device of claim 1,wherein the one or more blades is a plurality of blades.
 13. A medicaldispensing device, comprising: a catheter defining a lumen having alongitudinal axis and a distal opening; a plunger disposed in the lumenand movable along the longitudinal axis; a plurality of balls disposedin the lumen proximal to the distal opening and distal to the plunger,the plurality of balls being stacked along the longitudinal axis fordispersement, one ball at a time, through the distal opening via a forceapplied by the plunger; and one or more cutting elements disposed at thedistal opening, wherein an outer surface of each of the balls of theplurality of balls includes a first material surrounding and containingtherein a second material, wherein the one or more cutting elements isconfigured to cut the outer surface of each of the balls of theplurality of balls such that the second material is exposed as each ofthe balls of the plurality of balls is dispensed from the medicaldispensing device, and wherein the one or more cutting elements includesone or more blades.
 14. The medical dispensing device of claim 13,wherein the second material is one of a first reagent or a secondreagent.
 15. The medical dispensing device of claim 14, wherein a firstsubset of the plurality balls includes the first reagent, and wherein asecond subset of the plurality of balls includes the second reagent. 16.The medical dispensing device of claim 13, wherein the one or morecutting elements is configured to cut the outer surface of each of theballs of the plurality of balls such that the second material is exposedas each of the balls of the plurality of balls is dispensed from themedical dispensing device.
 17. The medical dispensing device of claim13, wherein a protrusion extends from a sidewall defining the lumen,toward the longitudinal axis, and distal to a distalmost ball of theplurality of balls.
 18. The medical dispensing device of claim 17,wherein the one or more cutting elements is disposed distal to theprotrusion.
 19. The medical dispensing device of claim 13, wherein theouter surface of each of the balls of the plurality of balls isdeformable.
 20. A method for delivering a reagent to tissue, the methodcomprising: pushing a stack of balls toward a distal opening of acatheter; advancing a distalmost ball of the stack of balls past aprotrusion disposed in a lumen of the catheter; cutting, with one ormore cutting elements, an outer surface of the distalmost ball, whereinthe one or more cutting elements includes one or more blades; andreleasing a reagent from an inner cavity of the distalmost ball.